New Heart Failure Guidelines

Darrell Hulisz, RPh, PharmDAllison Wetshtein

February 1, 2017

The American College of Cardiology (ACC), American Heart Association (AHA), and the Heart Failure Society of America (HFSA) recently updated the 2013 ACC/AHA guidelines for the management of heart failure. This update introduces two new pharmacological agents to the guidelines: 1) the combination product valsartan plus sacubitril (Entrsto), which is an angiotensin receptor-neprilysin inhbitor (ARNI) and 2) ivabradine (Corlanor), a sinoatrial node modulator.

Entresto contains the drug sacubitril, a prodrug that inhibits neprilysin, which causes a decrease in levels of peptides, including natriuretic peptides, bradykinin, adrenomedullin and other vasoactive peptides. Valsartan is an angiotensin receptor blocker (ARB) that blocks angiotensin II receptors, which produces vasodilation. The primary side effects of Entresto include hypotension, hyperkalemia, and renal insufficiency. The drug does carry a small risk of angioedema, and pharmacists should remind patients about this potential side effect. While Entrsto is unlikely to be used in women of child bearing potential, the drug can cause injury and death to the developing fetus. This drug, as well as other drugs acting on the renin-angiotensin-aldosterone system should be abruptly discontinued once pregnancy is confirmed.

Beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), and angiotensin receptor neprilysin (ARNI) have all been shown to decrease morbidity and mortality in heart failure patients. According to the new guidelines, ARNIs are acceptable alternatives to ACE inhibitors and ARBs in stable patients with symptomatic heart failure and reduced ejection fraction (HFrEF). The guidelines go even further to state that in patients with chronic symptomatic HFrEF, NYHA class II or III, who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality.

Before initiation of an ARNI, patients must first be able to tolerate an ACE inhibitor or ARB. ACE inhibitors must be stopped 36 hours before ARNIs can be initiated in patients because any overlap of therapy has been associated with an increased risk of angioedema and morbidity. Both ACE inhibitors and ARNI cause the breakdown of bradykinin, which can cause the adverse event of angioedema. An ARNI should not be administered to anyone who has a history of angioedema with use of an ACE inhibitor because it may increase the risk of recurrence of angioedema. The ARNI approved for use in heart failure due to clinical trials is sacubitril, which is made in a combination pill with valsartan in a study known as the PARADIGM-HF trial. The target dose of valsartan/sacubitril is 97/103 mg twice daily.

The second drug included in the heart failure guideline is ivabradine, a sinoatrial (SA) node inhibitor that is selective for f-channels, which slows the firing of the SA node and reduces the heart rate. It has been proven to be decrease heart failure-related hospitalizations in NYHA Class II-III heart failure patients with left ventricular ejection fraction (LVEF) of <35%. Ivabradine, however, has not proven to decrease morbidity or mortality for heart failure patients. Ivabradine should only be used in patients already on beta blockers that have titrated up to the target dose, as tolerated. These patients must also be in sinus rhythm with a heart rate of 70 bpm or greater. Ivabradine should be taken with meals. Adverse reactions include bradycardia, hypertension, atrial fibrillation, heart block, and sinoatrial arrest. This medications use is contraindicated in patients with blood pressure <90/50mmHg, sick sinus syndrome, third degree heart block, pacemaker dependence, hepatic impairment, and resting heart rate of less than 60 beats per minute.

To summarize, the guidelines where issued because treatment options for heart failure have expanded recently. The guidelines are evidence-based and provide recommendations that will guide clinicians on choice of therapy in an attempt to improve outcomes for patients with chronic heart failure.